23, 25, 26-trihydroxycholecalciferol. A 25-hydroxycholecalciferol-26,23-lactone precursor

Abstract

(235)-23,25-Dihydroxycholecalciferol was converted into at least five metabolites in kidney homogenates prepared from 1,25-dihydroxycholecalciferol-treated chickens. One of these has been positively identified as 23,25,26-trihydroxycholecalciferol by u.v.-absorbance analysis, mass spectrometry and chemical formation of derivatives. 23,25,26-Trihydroxycholecalciferol produces when incubated in chick kidney homogenates.The major circulating metabolite of cholecalciferol is 25(OH)D3 (Hadded et al., 1977; Horst et aL, 198 la,b). 25(OH)D3-lactone is a significant 25(OH)D3 metabolite in animals receiving large doses of cholecalciferol (Wichmann et al., 1979;Horst, 1979). This lactone has a 5-fold higher affinity for the vitamin D serum carrier protein than does 25(OH)D3 (Horst & Littledike, 1980

The stereochemical configuration of the natural 23,25,26‐trihydroxyvitamin D3

“…Our data unquestionably demonstrate that the naturally-occurring stereoisomer of 23,25,26(OH)sDs has the 23(s) and 25(R) configuration. These data are further substantiated in [16,18] where 23,25,26(OH)sD3 was metabolized to 23(S),25(R)-25-OH-D3-26,23-lactone.…”

“…[12,13], and 23(S),25(OH)zDs is metabolized to 23,25, 26(OH)sD3 [18], On the other hand, 25,26(OH)zDs possesses the 25(S) absolute configuration [24]. With 25(5),26(OH)zDr as a precursor, stereochemical inversion of the hydroxyl group at the C-25 position must occur during the course of C-23 hydroxylation.…”

“…It is possible that the 23,25,26(0H)sD3 can arise from 23,25(OH)~D3 [ll] or 25,26(OH)zDs 1231, a metabolite of vitamin Ds. The stereochemistry at the C-23 position of the natural 23,25(OH)zDs was determined to be the 23(s) configuration [12,13], and 23(S),25(OH)zDs is metabolized to 23,25, 26(OH)sD3 [18], On the other hand, 25,26(OH)zDs possesses the 25(S) absolute configuration [24]. With 25(5),26(OH)zDr as a precursor, stereochemical inversion of the hydroxyl group at the C-25 position must occur during the course of C-23 hydroxylation.…”

A new insight into the role of rat cytochrome P450 24A1 in metabolism of selective analogs of 1α,25-dihydroxyvitamin D3

“…Of these metabolic pathways, 1 mainly proceeds through C24 oxidation pathway which is initiated by C24 hydroxylation, followed by a series of side chain oxidations leading to the formation of the final metabolite, calcitroic acid [11–13]. The remaining two pathways initiated by C23 and C26 hydroxylations are minor metabolic pathways responsible for conversion of 1 to the final metabolite, calcitriol lactone [14]. For a comprehensive overview on vitamin D metabolism and the enzymes involved, the reader is referred to a recent review [15].…”

Structures and biological activities of vitamin D metabolites and their analogs

“…The 26-trifluoro (92) and 26,27-hexafluoro analogs (93) were tested by Stern224,225 for their activities (1) in competing with 1,25-(OH)2D3 for binding to partially purified chick intestinal cytosol, (2) With the discovery of 25-OH-D3-26,23-lactone and 23,25-(OH)2D3 as the major metabolites of 25-OH-D3 came to realization that an important pathway of vitamin D metabolism involves 23-hydroxylation. Both the lactone and 23,25-(OH)2D3 have little biological activity, but their possible functional role cannot be completely excluded on this basis.…”